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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04662710




Registration number
NCT04662710
Ethics application status
Date submitted
4/12/2020
Date registered
10/12/2020

Titles & IDs
Public title
Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) Plus Chemotherapy in Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma (MK-7902-015/E7080-G000-321/LEAP-015)
Scientific title
Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) Plus Chemotherapy Compared With Standard of Care Therapy as First-line Intervention in Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma (LEAP-015)
Secondary ID [1] 0 0
MK-7902-015
Secondary ID [2] 0 0
7902-015
Universal Trial Number (UTN)
Trial acronym
LEAP-015
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced/Metastatic Gastroesophageal Adenocarcinoma 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Other - Lenvatinib
Treatment: Drugs - Oxaliplatin
Treatment: Drugs - Capecitabine
Treatment: Drugs - Leucovorin (or Levoleucovorin)
Treatment: Drugs - 5-FU

Experimental: Lenvatinib + Pembrolizumab + Chemotherapy - Participants receive lenvatinib administered orally (PO) every day (QD) in combination with pembrolizumab intravenously (IV) every 6 weeks (Q6W) plus chemotherapy with either capecitabine and oxaliplatin (CAPOX) or chemotherapy with 5-FU, leucovorin, and oxaliplatin (mFOLFOX6). Induction with lenvatinib 8 mg QD plus pembrolizumab (400 mg Q6W) plus chemotherapy (CAPOX or mFOLFOX6) will be administered for 2 cycles (approximately 12 weeks), followed by consolidation with lenvatinib 20 mg QD plus pembrolizumab (400 mg Q6W) for 16 cycles. A cycle is 6 weeks (42 days).

Experimental: Chemotherapy - Participants receive chemotherapy with either CAPOX Q3W or mFOLFOX6 Q2W. A cycle is 6 weeks (42 days).


Treatment: Other: Pembrolizumab
400 mg Q6W by IV infusion

Treatment: Other: Lenvatinib
Administered PO QD, 8 mg induction/20 mg consolidation.

Treatment: Drugs: Oxaliplatin
130 mg/m\^2 administered by IV infusion on Day 1 of Weeks 1 and 4 of each Q6W cycle as part of CAPOX chemotherapy, or 85 mg/m\^2 administered by IV infusion on Day 1 and Week 1, 3 and 5 of each Q6W cycle as part of mFOLFOX6 chemotherapy.

Treatment: Drugs: Capecitabine
1000 mg/m\^2 administered PO twice daily (BID) on Days 1-14, 22-35 of each Q6W cycle as part of CAPOX chemotherapy.

Treatment: Drugs: Leucovorin (or Levoleucovorin)
Administered by IV infusion at 400 mg/m\^2 (leucovorin) or 200 mg/m\^2 (levoleucovorin) on Day 1, and Week 1, 3 and 5 of each Q6W cycle as part of mFOLFOX6 chemotherapy.

Treatment: Drugs: 5-FU
400 mg/m\^2 bolus IV infusion followed by 2400 mg/m\^2 continuous IV infusion administered on Day 1, and Week 1, 3, 5, of each Q2W cycle as part of mFOLFOX6 chemotherapy.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to ~21 days
Primary outcome [2] 0 0
Part 1: Number of Participants with Adverse Events (AEs)
Timepoint [2] 0 0
Up to ~28 months
Primary outcome [3] 0 0
Part 1: Number of Participants who Discontinued Study Treatment Due to an AE
Timepoint [3] 0 0
Up to ~25 months
Primary outcome [4] 0 0
Part 2: Overall Survival (OS) in Participants with Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) =1
Timepoint [4] 0 0
Up to ~41 months
Primary outcome [5] 0 0
Part 2: OS in All Participants
Timepoint [5] 0 0
Up to ~41 months
Primary outcome [6] 0 0
Part 2: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants with PD-L1 CPS =1
Timepoint [6] 0 0
Up to ~31 months
Primary outcome [7] 0 0
Part 2: PFS Per RECIST 1.1 as Assessed by BICR in All Participants
Timepoint [7] 0 0
Up to ~31 months
Secondary outcome [1] 0 0
Part 2: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS =1
Timepoint [1] 0 0
Up to ~31 months
Secondary outcome [2] 0 0
Part 2: ORR Per RECIST 1.1 as Assessed by BICR in All Participants
Timepoint [2] 0 0
Up to ~31 months
Secondary outcome [3] 0 0
Part 2: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS =1
Timepoint [3] 0 0
Up to ~31 months
Secondary outcome [4] 0 0
Part 2: DOR Per RECIST 1.1 as Assessed by BICR in All Participants
Timepoint [4] 0 0
Up to ~31 months
Secondary outcome [5] 0 0
Part 2: Number of Participants with AEs
Timepoint [5] 0 0
Up to ~28 months
Secondary outcome [6] 0 0
Part 2: Number of Participants who Discontinued Study Treatment Due to an AE
Timepoint [6] 0 0
Up to ~25 months

Eligibility
Key inclusion criteria
* Has histologically and/or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic gastroesophageal adenocarcinoma
* Is not expected to require tumor resection during the treatment course
* Has gastroesophageal adenocarcinoma that is not HER-2/neu positive
* Has measurable disease as defined by RECIST 1.1 by scan with IV contrast as determined by the local site investigator
* Male participants agree to refrain from donating sperm and agree to either remain abstinent from heterosexual intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for =7 days after last dose of lenvatinib or 90 days after last dose of chemotherapy-whichever comes last
* Female participants not pregnant or breastfeeding are eligible to participate if not a women of childbearing potential (WOCBP), or if a WOCBP they either use a contraceptive method that is highly effective OR remain abstinent from heterosexual intercourse as their preferred and usual lifestyle, and do not donate eggs (ova, oocytes) to others or freeze/store for their own use, and abstain from breastfeeding during the intervention period through 120 days after last dose of pembrolizumab, 30 days after last dose of lenvatinib, or 180 days after last dose of chemotherapy-whichever occurs last
* Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of study treatment
* Has adequately controlled blood pressure with or without antihypertensive medications
* Has adequate organ function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ) esophageal adenocarcinoma
* Has had major surgery within 28 days prior to first dose of study interventions
* Has had radiotherapy within 14 days of randomization
* Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
* Has known CNS metastases and/or carcinomatous meningitis
* Has severe hypersensitivity (=Grade 3) to treatment with an monoclonal antibody (mAb) or known sensitivity or intolerance to any component of lenvatinib, pembrolizumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum containing products
* Has had an allogeneic tissue/solid organ transplant
* Has perforation risks or significant gastrointestinal (GI) bleeding
* Has GI obstruction, poor oral intake (CAPOX participants), or difficulty in taking oral medication (CAPOX participants)
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
* Has received prior therapy with anti- vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor or anti-VEGF mAb
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug
* Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
* Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
* Has inadequate cardiac function
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has poorly controlled diarrhea
* Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment.
* Has peripheral neuropathy =Grade 2
* Has a known history of human immunodeficiency virus (HIV) or HIV 1/2 antibodies
* Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
* Has weight loss of >20% within the last 3 months

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
2/02/2026
Actual
Sample size
Target
890
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Nepean Hospital ( Site 2305) - Kingswood
Recruitment hospital [2] 0 0
Wollongong Hospital ( Site 2307) - Wollongong
Recruitment hospital [3] 0 0
Royal Brisbane and Women s Hospital ( Site 2304) - Herston
Recruitment hospital [4] 0 0
Hollywood Private Hospital-Medical Oncology ( Site 2308) - Nedlands
Recruitment postcode(s) [1] 0 0
2747 - Kingswood
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
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Pennsylvania
Country [10] 0 0
Argentina
State/province [10] 0 0
Buenos Aires
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Argentina
State/province [11] 0 0
Cordoba
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Belgium
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Namur
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Belgium
State/province [13] 0 0
Oost-Vlaanderen
Country [14] 0 0
Belgium
State/province [14] 0 0
Vlaams-Brabant
Country [15] 0 0
Belgium
State/province [15] 0 0
West-Vlaanderen
Country [16] 0 0
Canada
State/province [16] 0 0
Nova Scotia
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
Chile
State/province [19] 0 0
Araucania
Country [20] 0 0
Chile
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Coquimbo
Country [21] 0 0
Chile
State/province [21] 0 0
Maule
Country [22] 0 0
Chile
State/province [22] 0 0
Region M. De Santiago
Country [23] 0 0
China
State/province [23] 0 0
Anhui
Country [24] 0 0
China
State/province [24] 0 0
Beijing
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China
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Fujian
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China
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Gansu
Country [27] 0 0
China
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Guangdong
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China
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Hainan
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China
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Hebei
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China
State/province [30] 0 0
Heilongjiang
Country [31] 0 0
China
State/province [31] 0 0
Henan
Country [32] 0 0
China
State/province [32] 0 0
Hubei
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China
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Hunan
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China
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Jiangsu
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China
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Jilin
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China
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Shaanxi
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China
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Shandong
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China
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Shanghai
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China
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Tianjin
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Xinjiang
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China
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Zhejiang
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Colombia
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Atlantico
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Colombia
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Cesar
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Colombia
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Cordoba
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Colombia
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Distrito Capital De Bogota
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Colombia
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Narino
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Colombia
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Risaralda
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Costa Rica
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San Jose
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France
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Calvados
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France
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Cote-d Or
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Gironde
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Haute-Savoie
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France
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Pays-de-la-Loire
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Rhone-Alpes
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France
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Val-de-Marne
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Vaucluse
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France
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Paris
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Germany
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Bayern
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Germany
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Hessen
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Germany
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Niedersachsen
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Germany
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Sachsen
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Germany
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Berlin
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Germany
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Hamburg
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Guatemala
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Guatemala
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Hong Kong
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Hong Kong
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Ireland
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Leinster
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Ireland
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Dublin
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Israel
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Be'er Sheva
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Israel
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Hadera
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Kfar-Saba
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Israel
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Petah Tikva
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Israel
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Tel Aviv
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Italy
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Abruzzo
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Italy
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Friuli-Venezia Giulia
Country [77] 0 0
Italy
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Lombardia
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Italy
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Veneto
Country [79] 0 0
Italy
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Catanzaro
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Italy
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Milano
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Italy
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Napoli
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Japan
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Aichi
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Japan
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Chiba
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Japan
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Ehime
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Japan
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Hyogo
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Japan
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Ibaraki
Country [87] 0 0
Japan
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Kagawa
Country [88] 0 0
Japan
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Kanagawa
Country [89] 0 0
Japan
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Osaka
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Japan
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Saitama
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Japan
State/province [91] 0 0
Fukuoka
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Japan
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Hiroshima
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Japan
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Tokyo
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Korea, Republic of
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Kyonggi-do
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Korea, Republic of
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Seoul
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Korea, Republic of
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Taejon-Kwangyokshi
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Poland
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Dolnoslaskie
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Poland
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Mazowieckie
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Poland
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Podkarpackie
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Poland
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Wielkopolskie
Country [101] 0 0
Russian Federation
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Chelyabinskaya Oblast
Country [102] 0 0
Russian Federation
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Moskva
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Russian Federation
State/province [103] 0 0
Samarskaya Oblast
Country [104] 0 0
Russian Federation
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Sankt-Peterburg
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Russian Federation
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Yaroslavskaya Oblast
Country [106] 0 0
Spain
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Asturias
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Spain
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Cantabria
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Spain
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Barcelona
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Spain
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Madrid
Country [110] 0 0
Taiwan
State/province [110] 0 0
Taichung
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Taiwan
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Tainan
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Taiwan
State/province [112] 0 0
Taipei
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Taiwan
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Taoyuan
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Turkey
State/province [114] 0 0
Istanbul
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Turkey
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Ankara
Country [116] 0 0
Turkey
State/province [116] 0 0
Edirne
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Turkey
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Erzurum
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Turkey
State/province [118] 0 0
Izmir
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Cambridgeshire
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United Kingdom
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Dundee City
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United Kingdom
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Glasgow City
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United Kingdom
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London, City Of
Country [123] 0 0
United Kingdom
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Surrey
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United Kingdom
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Warwickshire
Country [125] 0 0
United Kingdom
State/province [125] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eisai Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04662710